The present invention relates, in general, to a process for separating optical isomers, i.e., the enantiomers and diastereomers of a compound, and in particular, to a process and apparatus for separating the optical isomers by an adsorptive bubble technique.
Approximately 35% of all pharmaceutical products and agrochemicals (pesticides, herbicides, etc.) are racemic mixtures. In many instances, one of the isomers present in these mixtures have undesired effects and limit the overall effectiveness of the active species. For example, one of the isomers may present toxicity concerns, biodistribution problems, altered metabolism, and unwanted interactions.
Various techniques have been proposed to separate the enantiomers present in these racemic mixtures. According to one of these techniques, a diastereomeric derivative or complex of the racemate with a pure chiral molecule (selector) is prepared and this mixture is recrystallized several times. Although this technique works well for some mixtures, it tends to be tedious, time consuming and has narrow applicability. Also, it requires one additional separation step; the chiral selector (used to achieve the separation) must be removed from the final product.
Another technique which has been proposed to separate the enantiomers present in these racemic mixtures is biological or enzymatic resolution. In this technique, microorganisms or enzymes are used which preferentially degrade or react with one enantiomer of a racemate. Although selective, this approach is practical with only a limited number of compounds where the appropriate enzymes are available.
Differential complexation of a variety of isomers by an immobilized chiral stationary phase has also been proposed for separating enantiomers from a racemic mixture. See, for example, Armstrong, Analytical Chemistry, 59:84a-91a (Jan. 1987) and Armstrong et al., Science, 232:1132-1135 (1986). In these articles, the use of immobilized .beta.-cyclodextrin and several other chiral stationary phases is reported for the enrichment of numerous compounds from such clinically useful classes as .beta.-blockers, calcium-channel blockers, sedative hypnotics, antihistamines, anticonvulsants, diuretics, and synthetic opiates. Although this approach has applicability for a wide range of compounds, especially for analytical-scale separations, effective scale-up to relatively large amounts (i.e., industrial scale) is difficult, sensitive and expensive and requires trained personnel.